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Review

GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review

1
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, 142-8555 Tokyo, Japan
2
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, 830-0011 Fukuoka, Japan
3
Diabetes Center, Ebina General Hospital, Ebina, 243-0433 Kanagawa, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1509; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041509
Received: 12 February 2020 / Revised: 20 February 2020 / Accepted: 21 February 2020 / Published: 22 February 2020
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that are secreted from enteroendocrine L cells and K cells in response to digested nutrients, respectively. They are also referred to incretin for their ability to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner. Furthermore, GLP-1 exerts anorexic effects via its actions in the central nervous system. Since native incretin is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), DPP-resistant GLP-1 receptor agonists (GLP-1RAs), and DPP-4 inhibitors are currently used for the treatment of type 2 diabetes as incretin-based therapy. These new-class agents have superiority to classical oral hypoglycemic agents such as sulfonylureas because of their low risks for hypoglycemia and body weight gain. In addition, a number of preclinical studies have shown the cardioprotective properties of incretin-based therapy, whose findings are further supported by several randomized clinical trials. Indeed, GLP-1RA has been significantly shown to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes. However, the role of GIP in cardiovascular disease remains to be elucidated. Recently, pharmacological doses of GIP receptor agonists (GIPRAs) have been found to exert anti-obesity effects in animal models. These observations suggest that combination therapy of GLP-1R and GIPR may induce superior metabolic and anti-diabetic effects compared with each agonist individually. Clinical trials with GLP-1R/GIPR dual agonists are ongoing in diabetic patients. Therefore, in this review, we summarize the cardiovascular effects of GIP and GIPRAs in cell culture systems, animal models, and humans. View Full-Text
Keywords: animal model; atherosclerosis; cardiac remodeling; GIP; restenosis animal model; atherosclerosis; cardiac remodeling; GIP; restenosis
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MDPI and ACS Style

Mori, Y.; Matsui, T.; Hirano, T.; Yamagishi, S.-i. GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review. Int. J. Mol. Sci. 2020, 21, 1509. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041509

AMA Style

Mori Y, Matsui T, Hirano T, Yamagishi S-i. GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review. International Journal of Molecular Sciences. 2020; 21(4):1509. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041509

Chicago/Turabian Style

Mori, Yusaku, Takanori Matsui, Tsutomu Hirano, and Sho-ichi Yamagishi. 2020. "GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review" International Journal of Molecular Sciences 21, no. 4: 1509. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041509

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